title: Pharmacokinetics and pharmacodynamics of intravenous daptomycin during continuous ambulatory peritoneal dialysis.
abstract: OBJECTIVE
  This study sought to (1) characterize the pharmacokinetic (PK) profile of intravenous (i.v.) daptomycin among patients receiving continuous ambulatory peritoneal dialysis (CAPD); (2) identify optimal i.v. CAPD dosing schemes; and (3) determine extent of daptomycin penetration into the peritoneal space after i.v. administration.
  
  
  METHODS
  A PK study was conducted among eight CAPD patients. Population PK modeling and Monte Carlo simulation (MCS) were used to identify CAPD dosing schemes providing efficacy and toxicity plasma profiles comparable with those obtained from MCS using the daptomycin population PK model derived from patients in the Staphylococcus aureus bacteremia-infective endocarditis (SAB-IE) study. The primary efficacy exposure target was the area under the curve (AUC). For toxicity, the goal was to identify CAPD dosing schemes that minimized plasma trough concentrations in excess of 24.3 mg/L. Finally, peritoneal cavity penetration was determined.
  
  
  RESULTS
  Administration of i.v. daptomycin 4 or 6 mg/kg, depending on indication, every 48 h was identified as the optimal CAPD dosing scheme. This regimen provided cumulative (AUC(0-48)) and daily partitioned (AUC(0-24 h) and AUC(24-48 h)) plasma AUC values similar to the SAB-IE or "typical patient" simulations. In addition, the proportion of patients likely to experience an elevated trough concentration in excess of 24.3 mg/L was similar between every 48 h CAPD dosing and the referent group. Penetration into the peritoneal cavity was 6% of plasma.
  
  
  CONCLUSIONS
  Daptomycin 4 or 6 mg/kg, on the basis of indication, i.v. every 48 h was found to be the optimal i.v. CAPD dosing scheme.
authors.affiliation: Albany College of Pharmacy and Health Sciences, 106 New Scotland Avenue, Albany, NY 12208, USA.
authors.forename: Katie E
authors.initials: KE
authors.lastname: Cardone
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Lodise
authors.forename: Nimish
authors.initials: N
authors.lastname: Patel
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Hoy
authors.forename: Shari
authors.initials: S
authors.lastname: Meola
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Manley
authors.forename: George L
authors.initials: GL
authors.lastname: Drusano
authors.forename: Darren W
authors.initials: DW
authors.lastname: Grabe
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D016470:Bacteremia / Q000517:prevention & control*; D017576:Daptomycin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004697:Endocarditis, Bacterial / Q000517:prevention & control; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D008875:Middle Aged; D008954:Models, Biological; D009010:Monte Carlo Method; D010529:Peritoneal Cavity; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000379:methods*; D013203:Staphylococcal Infections / Q000517:prevention & control
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin